40-23: Hereditary Hemorrhagic Telangiectasia

A. Symptoms and Signs

Hereditary hemorrhagic telangiectasia (HHT), formerly termed “Osler-Weber-Rendu syndrome,” is an autosomal dominant disorder of development of the vasculature. Epistaxis may begin in childhood or later in adolescence. Punctate telangiectases of the lips, tongue, fingers, and skin generally appear in later childhood and adolescence. Arteriovenous malformations (AVMs) can occur at any age in the brain, lungs, and liver. Bleeding from the gastrointestinal tract is due to mucosal vascular malformations (eFigures 40–7 and 40–8) and usually is not a problem until mid-adult years or later. Pulmonary AVMs can cause hypoxemia (with peripheral cyanosis, dyspnea, and clubbing) and right-to-left shunting (with embolic stroke or brain abscess). The criteria for diagnosis require presence of three of the following four features: (1) recurrent epistaxis, (2) visceral AVMs, (3) mucocutaneous telangiectases, and (4) being the near relative of a clearly affected individual. Mutation analysis can be used for presymptomatic diagnosis or exclusion of the worry of HHT.

B. Laboratory Findings

MR or CT arteriography detects AVMs. Mutations in at least five genes can cause HHT. Three have been identified, and molecular analysis to identify them is available; these mutations in ENG, ALK1, and SMAD4 account for about 87% of families with HHT. When the familial mutation is known, molecular testing is far more cost effective than repeated clinical screening of relatives who are at risk.

Embolization of pulmonary AVMs with wire coils or other occlusive devices reduces the risk of stroke and brain abscess. Treatment of brain AVMs reduces the risk of hemorrhagic stroke. All patients with HHT with evidence of a pulmonary shunt should practice routine endocarditis prophylaxis (see Table 33–5). All intravenous lines (except those for transfusion of red blood cells and radiographic contrast) should have an air-filter to prevent embolization of an air bubble. Prenatal diagnosis through mutation detection is possible.

All patients in whom the diagnosis of HHT is considered should have an MRI of the brain with contrast. A contrast echocardiogram will detect most pulmonary AVMs when “bubbles” appear on the left side of the heart after 3–6 cardiac cycles. A positive contrast echocardiogram should be followed by a high-resolution CT angiogram for localization of pulmonary AVMs. Patients who have AVMs with a feeding artery of 2 mm diameter or greater should undergo embolization. After successful embolization of all treatable pulmonary AVMs, the CT angiogram should be repeated in 6 months and 3 years. A person with a negative contrast echocardiogram should have the test repeated every 5 years. Any person with a pulmonary AVM, even an embolized one, should utilize routine endocarditis prophylaxis. Several studies suggest that treatment with anti-estrogenic agents (eg, tamoxifen), thalidomide or its relatives, or anti-vascular endothelial growth factor agents (eg, bevacizumab) can reduce epistaxis and gastrointestinal bleeding and improve hepatic shunting. However, two randomized, controlled clinical trials of intranasal bevacizumab therapy failed to show an improvement in epistaxis.